Hydroxychloroquine may be beneficial in preeclampsia and recurrent miscarriage

Abstract

Recurrent miscarriage (RM) and vasculoplacental disorders, such as preeclampsia (PE), affect women of childbearing age worldwide. Vascular endothelial dysfunction and immunological impairment are associated with both RM and PE. To date, there is no effective or optimal therapeutic approach for these conditions. Notably, aspirin use is only partially effective in the prevention of PE. Hydroxychloroquine (HCQ) has demonstrated beneficial effects on disease flares, pregnancy outcomes and cardiovascular impairment in systemic erythaematosus lupus (SLE) through its immunomodulatory, vasculoprotective and antithrombotic properties. Here, in the context of the underlying physiological dysregulation associated with PE and RM, the beneficial properties and potential therapeutic efficacy of HCQ are reviewed in anticipation of the results of current and future trials. Two related trials addressing RM in the absence of maternal autoimmune disease are ongoing. Other trials addressing pregnancy outcomes in the presence of maternal autoimmune disease are forthcoming. In this review, we hypothesise that the immunological and endothelial effects of HCQ may be beneficial in the context of PE and RM, regardless of the maternal autoimmune status. K E Y W O R D S hydroxychloroquine, pregnancy, preeclampsia, recurrent miscarriage

Impact of hydroxychloroquine on the gestational outcomes of pregnant women with immune system problems that necessitate the use of the drug

“…Moreover, the use of HCQ for COVID‐19 is especially not recommended outside of the hospital settings due to the risk of heart rhythm problems. On the contrary, HCQ treatment is needed to control maternal diseases, such as SLE, SS and RA, and decrease the risk of maternal complications such as thrombosis and congenital heart block 34,39–43 . It has also been reported that HCQ may directly be beneficial in obstetric complications such as preeclampsia and recurrent miscarriage 40 .…”

“…On the contrary, HCQ treatment is needed to control maternal diseases, such as SLE, SS and RA, and decrease the risk of maternal complications such as thrombosis and congenital heart block 34,39–43 . It has also been reported that HCQ may directly be beneficial in obstetric complications such as preeclampsia and recurrent miscarriage 40 . Adverse gestational and neonatal outcomes have not been associated with daily maternal doses of HCQ ≤400 mg 21,23,24 …”

“…On the contrary, HCQ treatment is needed to control maternal diseases, such as SLE, SS and RA, and decrease the risk of maternal complications such as thrombosis and congenital heart block. 34,[39][40][41][42][43] It has also been reported that HCQ may directly be beneficial in obstetric complications such as preeclampsia and recurrent miscarriage. 40 Adverse gestational and neonatal outcomes have not been associated with daily maternal doses of HCQ ≤400 mg. 21,23,24 In conclusion, low-dose low-molecular-weight heparin, low-dose salicylic acid and low-dose corticosteroid prophylaxis, together with low dose HCQ, seem to be reliable in high-risk pregnancies with immune system disorders such as SLE, SS and RA.…”

Low incidence of intrauterine growth restriction in pregnant patients with systemic lupus erythematosus taking hydroxychloroquine

“…The antithrombotic action of HCQ [25] may increase placental perfusion and fetal growth. However, HCQ efficacy on very early stages of pregnancy-and possibly in the preconceptional phase-suggests that other mechanisms are involved, including the regulation of complement activity [53], the maintenance of the action of physiological anticoagulants, such as Annexin 5 [29] and modulation of the inflammatory response which is fundamental for successful pregnancy [22]. Further studies are needed to define the mechanisms involved in the protective action of HCQ in pregnant patients.…”

“…Drugs compatible with pregnancy in SLE include hydroxychloroquine (HCQ) [20]. HCQ anti-inflammatory effect stems from interference with intracellular Toll-like receptors [21], with phospholipase activity and with the inflammatory cytokines production, thus promoting the TH2 shift typical of a normal pregnancy [22]. Moreover, the agent inhibits platelet aggregation and secretion of arachidonic acid by activated platelets [23,24], decreases the risk of thrombosis and increases overall survival in patients with SLE [25,26].…”